The potential pathophysiological role of tissue factor in age-related macular degeneration

Evidence for enhanced tissue factor expression in age-related macular degeneration

“…Recent studies have suggested the possibility that TF may be implicated in the pathogenesis of AMD 14. Immunostaining revealed TF expression in RPE cells and macrophages in post-mortem eyes with CNV and in surgically excised CNV specimens,21 TF was expressed strongly in macrophages and variably in RPE cells.…”

“…Studies have found an association of AMD with single-nucleotide polymorphisms of the genes coding for complement factor H, factor B, C2, and C3 1, 9. Of interest, coagulation factor X and fibrinogen, which are downstream mediators of blood coagulation closely related to the expression of TF activity, have been detected in AMD lesions as well 10–14. Inflammation elicited by lipopolysaccharide (LPS), TNF-α, IL-1, IL-6, C5a, and many other factors can result in increased cellular expression of TF.…”

“… 1 , 9 Of interest, coagulation factor X and fibrinogen, which are downstream mediators of blood coagulation closely related to the expression of TF activity, have been detected in AMD lesions as well. 10 – 14 Inflammation elicited by lipopolysaccharide (LPS), TNF-α, IL-1, IL-6, C5a, and many other factors can result in increased cellular expression of TF. Enhanced TF expression may in turn induce expression of pro-inflammatory cytokines such as IL-1β, IL-6, IL-8, and macrophage inflammatory protein-2α (MIP-2α/CXCL2α).…”

A Phase 1, Open-Label, Dose-Escalation Trial to Investigate Safety and Tolerability of Single Intravitreous Injections of ICON-1 Targeting Tissue Factor in Wet AMD

“…The TF/VIIa complex also mediates intracellular signaling through protease-activated receptors, and promotes inflammation mediated by TNF-a, IL-1, IL-6, IL-8, MIP-2a/CXCL2a, C5a, and other proinflammatory and proangiogenic cytokines. [6][7][8][9][10][11][12] TF is undetectable on normal ocular blood vessels, but its enhanced expression in nAMD has been reported by Cho et al 6 These findings implicate TF as a key molecular contributor of the inflammatory and angiogenic processes underlying nAMD. Prior findings suggest that proinflammatory cytokines and VEGF in turn stimulate expression of TF on the choroidal neovasculature, and that such reciprocal, stimulatory molecular interactions perpetuate the neovascular pathology of AMD and contribute to the continuous progression of the disease.…”

“…Prior findings suggest that proinflammatory cytokines and VEGF in turn stimulate expression of TF on the choroidal neovasculature, and that such reciprocal, stimulatory molecular interactions perpetuate the neovascular pathology of AMD and contribute to the continuous progression of the disease. 7 Interfering with TF-mediated signaling pathways may therefore provide a novel therapeutic approach for the treatment of nAMD, and potential to differentiate from the anti-VEGF agents by affecting the underlying CNV lesion progression.…”